The incidence of resistant hypertension, obesity, and obstructive sleep apnea (OSA), three highly prevalent conditions in the United States, is rising. Approximately one in three adults in the US has hypertension, and a significant proportion of these individuals have hypertension that is difficult to treat, or resistant. Obesity and OSA are well-established risk factors for resistant hypertension, a condition that portends significant cardiovascular risk. Awareness of the various mechanisms by which obesity and OSA impact systemic blood pressure is essential to better understand how best to effectively care for patients with resistant hypertension. In this review, we discuss the clinical and pathophysiologic associations between obesity, OSA, and resistant hypertension. Furthermore, we will explore the effect of continuous positive airway pressure therapy (CPAP) and other therapeutic interventions on blood pressure control in patients with resistant hypertension.Key Points• Obesity, obstructive sleep apnea, and resistant hypertension are highly prevalent conditions, with increasing overall incidence [1-3].• Both obesity and obstructive sleep apnea are independent risk factors for the development of resistant hypertension.• OSA is characterized by a physiologic cascade of collapse of the upper airway, which can lead to intermittent hypoxia, hypercapnia, significant negative intra-thoracic pressure, and increased SNS output.• Intermittent hypoxia leads to activation of the endothelin system [17, 18, 19•], which can lead to the development of resistant hypertension.• Intermittent hypoxia can lead to the over activation of the SNS, which can also contribute to the development of resistant hypertension [20, 21].• OSA leads to state of elevated adrenergic tone, which in turn may contribute to resistant hypertension [25-27].• OSA patients have a higher incidence of "non-dipping" of nocturnal systolic blood pressure, a marker of increased adrenergic tone. This potentially represents a risk factor for hypertensive end organ disease [31, 32].• The prevalence of OSA is significantly higher in patients predisposed to fluid accumulation: including kidney disease, heart failure and resistant hypertension [33].• Interventions (such as the daytime use of compression stocking) which reduce daytime lower extremity fluid accumulation can significantly reduce the severity of OSA, particularly in patients with comorbid resistant hypertension [35, 36].• CPAP therapy can significantly reduce blood pressure in patients with comorbid hypertension and OSA. The treatment effect is most pronounced in those with resistant hypertension and OSA [16••, 38-42].

The combination of glutamic acid decarboxylase (GAD) 65 antibodies (GADA) and protein tyrosine phosphatase-like protein IA2 antibodies (IA2-ab), measured by radioligand binding assays, has been suggested to replace islet cell antibodies (ICA), measured by indirect immunofluorescence, as a marker for autoimmune type I diabetes. The aim of this study was to compare the frequency of ICA and GADA and/or IA2-ab not only at, but also after the diagnosis of diabetes. ICA, GADA and IA2-ab were therefore assessed at and up to 11 y after the diagnosis of diabetes in 86 children (1-15-y-old). At diagnosis, ICA were found in 74 (86%) and GADA and/or IA2-ab in 79 (92%) of the diabetic children. Hence, there was no major difference in frequency between ICA and GADA and/or IA2-ab at diagnosis of diabetes. At follow-up, however, ICA were less frequent than GADA and/or IA2-ab; 1-3 y after diagnosis ICA were found in 12 (44%) and GADA and/or IA2-ab in 24 (89%) of 27 children (p=0.001); 4-6 y after diagnosis ICA were found in 7 (24%) and GADA and/or IA2-ab in 27 (93%) of 29 children (p < 0.0001); 7-11 y after diagnosis ICA were found in 4 (13%) and GADA and/or IA2-ab in 21 (70%) of 30 children (p < 0.0001). We conclude that the frequency of ICA does not always correspond to that of GADA and/or IA2-ab. Many years after diagnosis of diabetes, measurements of GADA and IA2-ab, but not ICA, detect autoimmunity in high frequency.

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The combination of glutamic acid decarboxylase (GAD) 65 antibodies (GADA) and protein tyrosine phosphatase‐like protein IA2 antibodies (IA2‐ab), measured by radioligand binding assays, has been suggested to replace islet cell antibodies (ICA), measured by indirect immunofluorescence, as a marker for autoimmune type 1 diabetes. The aim of this study was to compare the frequency of ICA and GADA and/or IA2‐ab not only at, but also after the diagnosis of diabetes. ICA, GADA and IA2‐ab were therefore assessed at and up to 11 y after the diagnosis of diabetes in 86 children (1‐15‐y‐old). At diagnosis, ICA were found in 74 (86%) and GADA and/or IA2‐ab in 79 (92%) of the diabetic children. Hence, there was no major difference in frequency between ICA and GADA and/or IA2‐ab at diagnosis of diabetes. At follow‐up, however, ICA were less frequent than GADA and/or IA2‐ab; 1–3 y after diagnosis ICA were found in 12 (44%) and GADA and/or IA2‐ab in 24 (89%) of 27 children (p = 0.001); 4–6 y after diagnosis ICA were found in 7 (24%) and GADA and/or IA2‐ab in 27 (93%) of 29 children (p < 0.0001); 7–11 y after diagnosis ICA were found in 4 (13%) and GADA and/or IA2‐ab in 21 (70%) of 30 children (p < 0.0001). We conclude that the frequency of ICA does not always correspond to that of GADA and/or IA2‐ab. Many years after diagnosis of diabetes, measurements of GADA and IA2‐ab, but not ICA, detect autoimmunity in high frequency.

Insulin autoantibodies are of less value compared with islet antibodies in the clinical diagnosis of autoimmune type 1 diabetes in children older than 3 yr of age.Borg, Henrik; Marcus, C; Sjöblad, Sture; Fernlund, Per; Sundkvist, Göran Link to publication Citation for published version (APA): Borg, H., Marcus, C., Sjöblad, S., Fernlund, P., & Sundkvist, G. (2002). Insulin autoantibodies are of less value compared with islet antibodies in the clinical diagnosis of autoimmune type 1 diabetes in children older than 3 yr of age. Pediatric Diabetes, 3(3), 149-54. DOI: 10.1034149-54. DOI: 10. /j.1399149-54. DOI: 10. -5448.2002 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal